Recanalization of the Native Artery in Patients with Bypass Failure

Our objective was to evaluate the possible role of endovascular recanalization of occluded native artery after a failed bypass graft in the case of either acute or chronic limb-threatening ischemia otherwise leading to amputation. In a single-center retrospective clinical analysis, from January 2004 to March 2007 we collected 31 consecutive high-surgical-risk patients (32 limbs) with critical limb ischemia following late ([30 days after surgery) failure of open surgery bypass graft reconstruction. All patients deemed unfit for surgery underwent tentative endovascular recanalization of the native occluded arterial tract. The mean follow-up period was 24 (range, 6–42) months. Technical success was achieved in 30 (93.7%) of 32 limbs. The cumulative primary assisted patency calculated by Kaplan–Meyer analysis was 92% and 88%, respectively, at 12 and 24 months. The limb salvage rate approached 90% at 30 months. In conclusion, our experience shows the feasibility of occluded native artery endovascular recanalization after a failed bypass graft, with optimal results in terms of midterm arterial patency and limb salvage. Our opinion is that successful recanalization of the arterial tract previously considered unsuitable for endovascular approach is allowed by improved competency and experience of vascular specialists, as well as the advances made in catheter and guidewire technology. This group of patients would previously have been relegated to repeat bypass grafts, with their inherently inferior patency and recognized added technical demands. We recognize previous surgical native artery disconnection and lack of pedal runoff to be the main cause of technical failure. Keywords Native artery Bypass failure Endovascular recanalizatio

Iminodiacetic acid (IDA) cation-exchange nonwoven membranes for efficient capture of antibodies and antibody fragments

There is strong need to reduce the manufacturing costs and increase the downstream purification efficiency of high-value therapeutic monoclonal antibodies (mAbs). This paper explores the performance of a weak cation-exchange membrane based on the coupling of IDA to poly(butylene terephthalate) (PBT) nonwoven fabrics. Uniform and conformal layers of poly(glycidyl methacrylate) (GMA) were first grafted to the surface of the nonwovens. Then IDA was coupled to the polyGMA layers under optimized conditions, resulting in membranes with very high permeability and binding capacity. This resulted in IgG dynamic binding capacities at very short residence times (0.1–2.0 min) that are much higher than those achieved by the best cation-exchange resins. Similar results were obtained in the purification of a single-chain (scFv) antibody fragment. As is customary with membrane systems, the dynamic binding capacities did not change significantly over a wide range of residence times. Finally, the excellent separation efficiency and potential reusability of the membrane were confirmed by five consecutive cycles of mAb capture from its cell culture harvest. The present work provides significant evidence that this weak cation-exchange nonwoven fabric platform might be a suitable alternative to packed resin chromatography for low-cost, higher productivity manufacturing of therapeutic mAbs and antibody fragments

Brain-derived neurotrophic factor (BDNF) and polysialylated-neural cell adhesion molecule (PSA-NCAM) in the human brainstem precerebellar nuclei from prenatal to adult age.

Occurrence and distribution of the neurotrophin brain-derived neurotrophic factor (BDNF) and polysialylated-neural cell adhesion molecule (PSA-NCAM), a neuroplasticity marker known to modulate BDNF signalling, were examined by immunohistochemistry in the human brainstem precerebellar nuclei at prenatal, perinatal and adult age. Western blot analysis performed in human brainstem showed for both molecules a single protein band compatible with the molecular weight of the dimeric form of mature BDNF and with that of PSA-NCAM. Detectability of both molecules up to 72 h post-mortem was also assessed in rat brain. In neuronal perikarya, BDNF-like immunoreactivity (LI) appeared as intracytoplasmic granules, whereas PSA-NCAM-LI appeared mostly as peripheral staining, indicative of membrane labelling; immunoreactivity to both substances also labelled nerve fibres and terminals. BDNF- and PSA-NCAM-LI occurred in the external cuneate nucleus, perihypoglossal nuclei, inferior olive complex, arcuate nucleus, lateral reticular formation, vestibular nuclei, pontine reticulotegmental and paramedian reticular nuclei, and pontine basilar nuclei. With few exceptions, for both substances the distribution pattern detected at prenatal age persisted later on, though the immunoreactivity appeared often higher in preand full-term newborns than in adult specimens. The results obtained suggest that BDNF operates in the development, maturation, maintenance and plasticity of human brainstem precerebellar neuronal systems. They also imply a multiple origin for the BDNF-LI of the human cerebellum. The codistribution of BDNF- and PSA-NCAM-LI in analyzed regions suggests that PSA-NCAM may modulate the functional interaction between BDNF and its high and low affinity receptors, an issue worth further analysis, particularly in view of the possible clinical significance of neuronal trophism in cerebellar neurodegenerative disorders.

Optimizing detection of RET and PPARg rearrangements in thyroid neoplastic cells using a home-brew tetracolor probe

BACKGROUND Fluorescence in situ hybridization (FISH) to identify specific DNA target sequences in the nuclei of nondividing cells of numerous solid neoplasms has contributed to the introduction of molecular cytogenetics as a useful adjunct to cytology, leading recently to the "marriage" of the 2 disciplines. Numerous cancer molecular markers can now be investigated using different technical approaches, at both the gene and expression levels, in biopsies of various suspected cancers, including differentiated thyroid carcinoma. The limited amount of bioptic material is often insufficient to carry out multiple tests, and optimizing handling of the biopsy is desirable. METHODS We have developed a home-brew tetracolor break-apart probe able to simultaneously identify the 2 most common genetic alterations in differentiated thyroid carcinoma: RET/PTC variants in papillary thyroid carcinoma and PAX8/PPARg fusion and variants in follicular thyroid carcinoma. RESULTS The probe had 100% specificity, 99.5% sensitivity, and >= 3% cutoff. The probe was tested on RET/PTC and PAX8/PPARg RT-PCR positive controls, and feasibility was assessed in 368 thyroid nodule fine-needle aspirations (FNA). In the latter analysis, 24 FNAs had split RET signal, and 9 had split PPARg signal. FISH analysis of available surgically removed nodules confirmed the sensitivity of FISH in detecting abnormal clones and oligoclones. CONCLUSIONS The home-brew tetracolor probe showed high feasibility, optimizing the use of the biological material in relation to the available molecular tests and maximizing the FISH experimental and slide-scoring times. This probe may be considered an alternative to RT-PCR when recovery and quality of RNA amplification from FNA are insufficient

Post Quantum Cryptography from Mutant Prime Knots

By resorting to basic features of topological knot theory we propose a (classical) cryptographic protocol based on the `difficulty' of decomposing complex knots generated as connected sums of prime knots and their mutants. The scheme combines an asymmetric public key protocol with symmetric private ones and is intrinsecally secure against quantum eavesdropper attacks.Comment: 14 pages, 5 figure

Research of Gravitation in Flat Minkowski Space

In this paper it is introduced and studied an alternative theory of gravitation in flat Minkowski space. Using an antisymmetric tensor, which is analogous to the tensor of electromagnetic field, a non-linear connection is introduced. It is very convenient for studying the perihelion/periastron shift, deflection of the light rays near the Sun and the frame dragging together with geodetic precession, i.e. effects where angles are involved. Although the corresponding results are obtained in rather different way, they are the same as in the General Relativity. The results about the barycenter of two bodies are also the same as in the General Relativity. Comparing the derived equations of motion for the $n$-body problem with the Einstein-Infeld-Hoffmann equations, it is found that they differ from the EIH equations by Lorentz invariant terms of order $c^{-2}$.Comment: 28 page

3D Analysis of Ordered Porous Polymeric Particles using Complementary Electron Microscopy Methods

Highly porous particles with internal triply periodic minimal surfaces were investigated for sorption of proteins. The visualization of the complex ordered morphology requires complementary advanced methods of electron microscopy for 3D imaging, instead of a simple 2D projection: transmission electron microscopy (TEM) tomography, slice-and-view focused ion beam (FIB) and serial block face (SBF) scanning electron microscopy (SEM). The capability of each method of 3D image reconstruction was demonstrated and their potential of application to other synthetic polymeric systems was discussed. TEM has high resolution for details even smaller than 1 nm, but the imaged volume is relatively restricted (2.5 \u3bcm)3. The samples are pre-sliced in an ultramicrotome. FIB and SBF are coupled to a SEM. The sample sectioning is done in situ, respectively by an ion beam or an ultramicrotome, SBF, a method so far mostly applied only to biological systems, was particularly highly informative to reproduce the ordered morphology of block copolymer particles with 32\u201354 nm nanopores and sampling volume (20 \u3bcm)3